Effect of Blood Sugar Control on the Accumulation of Sorbitol and Fructose in Nervous Tissues

Some products of the sorbitol metabolic pathway of glucose were extracted from peripheral nerves and spinal cords of rats, identified, and measured. Within a few days after a diabetic state was induced with streptozotocin, glucose, sorbitol, and fructose in nerve and cord had risen sharply as blood glucose increased. These levels were partially controlled when the blood sugar was restricted by insulin, but they increased rapidly when the insulin was withheld. Withdrawal of treatment resulted in a much greater rise of the fructose in the nervous system in animals that had been diabetic for six weeks before institution of treatment with insulin than in animals treated from induction. When phen-formin was used as a controlling agent in place of insulin, accumulation of glucose and fructose in the nervous system was enhanced, whereas fructose was found to decrease when tolbutamide was used. Earlier workers have shown that the sorbitol pathway seems to be associated with the Schwann cell and that dysfunction of this cell leads to segmental demyelination. We find that accumulation in nerves of the products of the sorbitol pathway may be minimized when blood sugar is controlled; since we have evidence that in human beings with diabetes good control improves the state of myelination of already damaged nerves, it is postulated that herein lies the mechanism whereby control of diabetes is likely to lead to a reduction in the incidence of nerve damage.